Clinical use of rVIII‑SingleChain in people with haemophilia A in Germany: Interim results from a prospective, non-interventional study

Introduction: Recombinant VIII (rVIII)‑SingleChain, a B‑domain truncated factor VIII (FVIII), is indicated for prophylaxis and on-demand treatment of bleeding in people with haemophilia A (PwHA). Although clinical studies have demonstrated the efficacy and tolerability of rVIII‑SingleChain in PwHA, real-world studies are warranted to determine the effectiveness and safety of rVIII‑SingleChain in routine clinical practice.

Method: Results are reported from a sub‑analysis of PwHA from Germany receiving rVIII‑SingleChain prophylaxis or on-demand treatment as a part of a non‑interventional study including PwHA from six European countries. All PwHA were eligible for enrolment between August 2019 and December 2021, and were followed up for up to three years. Annualised bleeding rate (ABR), annualised spontaneous bleeding rate (AsBR), infusion frequency, dosage, haemostatic effectiveness and safety were recorded. PwHA were excluded from efficacy analyses if they spent<12 weeks on a specific regimen. PwHA may be included in multiple treatment categories as they could switch treatment regimens.

Results: At the third interim data cut-off on 3^rd October 2023, the study had enrolled 43 previously treated PwHA. The mean (standard deviation [SD], range) age of PwHA was 32.7 (16.89, 8–78) years at enrolment, and the mean (SD) follow-up period was 30.0 (4.56) months. Patient characteristics are shown in [Fig. 1]. The median (interquartile range [IQR]) ABR and AsBR for PwHA on any prophylaxis regimen (n=37) were 0.42 (0.00–2.06) and 0.00 (0.00–1.55), respectively; mean (SD) ABR and AsBR were 1.5 (2.28) and 1.1 (1.88), respectively. For PwHA on 2x weekly prophylaxis (n=8), median (IQR) ABR and AsBR were 0.00 (0.00–0.48) and 0.00 (0.00–0.33), respectively; mean (SD) ABR and AsBR were 0.5 (1.04) and 0.3 (0.62), respectively. In both the prophylaxis and on-demand treatment groups, the majority of the reported bleeding episodes were mild (48.5% and 65.6%, respectively), with overall haemostatic effectiveness reported as excellent (51.7%) or good (33.3%) in PwHA who had data available from at least one assessment. Overall, 24 adverse events were reported in 14 PwHA, including five serious events, but all were considered unrelated to rVIII‑SingleChain. During treatment with rVIII‑SingleChain, no PwHA developed inhibitors to FVIII.

Fig. 1  Patient characteristics at baseline

Conclusion: This third interim analysis confirms that rVIII‑SingleChain is effective and well tolerated when used for prophylaxis or on-demand treatment in PwHA. The collection of data is ongoing to assess long‑term effectiveness and tolerability.